Flucytosine 250mg Capsules
WARNING: If you have kidney disease, talk to your doctor.Your doctor must closely watch your blood cells and kidney and liver function. @ COMMON USES: It is used to treat fungal infections.
Drug Class
Antifungal
Pharmacologic Class
Antimetabolite Antifungal
Pregnancy Category
Category C
FDA Approved
Aug 1971
DEA Schedule
Not Controlled
Overview
What is this medicine?
Flucytosine is an antifungal medicine used to treat serious fungal infections, especially those affecting the brain, spinal cord, or blood. It works by stopping the growth of the fungus. It is often used together with another antifungal medicine called amphotericin B.
How to Use This Medicine
Taking Your Medication Correctly
To use this medication safely and effectively, follow your doctor's instructions and read all the information provided. Take your medication as directed by your doctor or healthcare provider, even if you start to feel better.
To minimize stomach upset or nausea, consider taking a few capsules at a time over a 15-minute period. Continue taking your medication as prescribed, even if you feel well, to ensure the best possible outcome.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry location, avoiding bathrooms and areas where children and pets may access it. Keep all medications in a secure place to prevent accidental ingestion.
When disposing of unused or expired medication, do not flush it down the toilet or pour it down the drain unless specifically instructed to do so. Instead, consult your pharmacist for guidance on the proper disposal method. You may also want to explore local drug take-back programs for a safe and environmentally responsible way to dispose of your medication.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it is close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not take two doses at the same time or take extra doses to make up for the missed one.
To use this medication safely and effectively, follow your doctor's instructions and read all the information provided. Take your medication as directed by your doctor or healthcare provider, even if you start to feel better.
To minimize stomach upset or nausea, consider taking a few capsules at a time over a 15-minute period. Continue taking your medication as prescribed, even if you feel well, to ensure the best possible outcome.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry location, avoiding bathrooms and areas where children and pets may access it. Keep all medications in a secure place to prevent accidental ingestion.
When disposing of unused or expired medication, do not flush it down the toilet or pour it down the drain unless specifically instructed to do so. Instead, consult your pharmacist for guidance on the proper disposal method. You may also want to explore local drug take-back programs for a safe and environmentally responsible way to dispose of your medication.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it is close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not take two doses at the same time or take extra doses to make up for the missed one.
Lifestyle & Tips
- Take the capsules with food to help reduce stomach upset.
- Take doses at evenly spaced intervals throughout the day (e.g., every 6 hours) to maintain steady drug levels.
- Do not stop taking this medicine without consulting your doctor, even if you feel better, as the infection may return.
- Maintain good hydration unless otherwise advised by your doctor.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
50 to 150 mg/kg/day orally in 4 divided doses, administered at 6-hour intervals.
Dose Range:
50 - 150 mg
Condition-Specific Dosing:
cryptococcosis:
Often used in combination with amphotericin B. Initial dose typically 100-150 mg/kg/day.
candidiasis:
Often used in combination with amphotericin B. Initial dose typically 50-150 mg/kg/day.
Pediatric Dosing
Neonatal:
Not established (limited data, use with extreme caution and close monitoring).
Infant:
50 to 150 mg/kg/day orally in 4 divided doses, administered at 6-hour intervals (similar to adults, but adjust based on renal function and close monitoring).
Child:
50 to 150 mg/kg/day orally in 4 divided doses, administered at 6-hour intervals.
Adolescent:
50 to 150 mg/kg/day orally in 4 divided doses, administered at 6-hour intervals.
Dose Adjustments
Renal Impairment:
Mild:
CrCl 20-40 mL/min: 25-50 mg/kg every 12 hours.
Moderate:
CrCl 10-20 mL/min: 25-50 mg/kg every 24 hours.
Severe:
CrCl <10 mL/min: 25-50 mg/kg every 48 hours or longer, based on serum flucytosine levels.
Dialysis:
Hemodialysis: Administer 25-50 mg/kg after each dialysis session. Peritoneal Dialysis: Not well studied, but likely requires similar adjustments to severe renal impairment with close monitoring of serum levels.
Hepatic Impairment:
Mild:
No specific dose adjustment recommended, but monitor liver function tests.
Moderate:
No specific dose adjustment recommended, but monitor liver function tests.
Severe:
No specific dose adjustment recommended, but monitor liver function tests.
Pharmacology
Mechanism of Action
Flucytosine is an antifungal agent that is converted to 5-fluorouracil (5-FU) within susceptible fungal cells by the enzyme cytosine deaminase. Human cells lack this enzyme, which contributes to selective toxicity. 5-FU is then metabolized to 5-fluorodeoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). FdUMP inhibits thymidylate synthase, thereby interfering with fungal DNA synthesis. FUTP is incorporated into fungal RNA, disrupting protein synthesis.
Pharmacokinetics
Absorption:
Bioavailability:
80-90%
Tmax:
2-6 hours
FoodEffect:
Food delays the rate of absorption but does not significantly affect the extent of absorption.
Distribution:
Vd:
0.6 L/kg
ProteinBinding:
<5%
CnssPenetration:
Yes (achieves 75-80% of plasma concentrations in CSF)
Elimination:
HalfLife:
2.5-6 hours (prolonged significantly in renal impairment)
Clearance:
Primarily renal clearance, proportional to creatinine clearance
ExcretionRoute:
Renal
Unchanged:
Approximately 90% (excreted unchanged in urine)
Pharmacodynamics
OnsetOfAction:
Not acutely defined; therapeutic effects are observed over days to weeks of therapy.
PeakEffect:
Steady-state concentrations are typically achieved within 24-48 hours with normal renal function.
DurationOfAction:
Dependent on maintaining therapeutic concentrations; effects persist as long as drug is present.
Safety & Warnings
BLACK BOX WARNING
Extreme caution is advised in the administration of flucytosine to patients with bone marrow depression. Frequent monitoring of hematologic parameters (CBC with differential and platelets) and renal function is essential during therapy.
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash or hives
+ Itching or red, swollen, blistered, or peeling skin (with or without fever)
+ Wheezing or tightness in the chest or throat
+ Difficulty breathing, swallowing, or talking
+ Unusual hoarseness or swelling of the mouth, face, lips, tongue, or throat
Signs of bleeding, including:
+ Vomiting or coughing up blood
+ Vomit that resembles coffee grounds
+ Blood in the urine
+ Black, red, or tarry stools
+ Bleeding from the gums
+ Abnormal vaginal bleeding
+ Unexplained bruises or bruises that enlarge
+ Uncontrollable bleeding
Signs of kidney problems, such as:
+ Inability to urinate
+ Changes in urine output
+ Blood in the urine
+ Sudden weight gain
Signs of low potassium levels, including:
+ Muscle pain or weakness
+ Muscle cramps
+ Abnormal heartbeat
Signs of low blood sugar, such as:
+ Dizziness
+ Headache
+ Fatigue
+ Shaking
+ Rapid heartbeat
+ Confusion
+ Hunger
+ Sweating
Chest pain or pressure
Shortness of breath, sudden weight gain, or swelling in the arms or legs
Confusion
Hallucinations (seeing or hearing things that are not there)
Seizures
Mood changes
Mouth irritation or mouth sores
Hearing loss
Changes in balance
Abnormal burning, numbness, or tingling sensations
Shakiness, difficulty moving, or stiffness
Severe and potentially life-threatening liver problems, characterized by:
+ Dark urine
+ Fatigue
+ Decreased appetite
+ Nausea or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it is essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other unusual symptoms, contact your doctor or seek medical help:
Drowsiness
Dry mouth
Stomach pain or diarrhea
Nausea or vomiting
Decreased appetite
Headache
Fatigue or weakness
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash or hives
+ Itching or red, swollen, blistered, or peeling skin (with or without fever)
+ Wheezing or tightness in the chest or throat
+ Difficulty breathing, swallowing, or talking
+ Unusual hoarseness or swelling of the mouth, face, lips, tongue, or throat
Signs of bleeding, including:
+ Vomiting or coughing up blood
+ Vomit that resembles coffee grounds
+ Blood in the urine
+ Black, red, or tarry stools
+ Bleeding from the gums
+ Abnormal vaginal bleeding
+ Unexplained bruises or bruises that enlarge
+ Uncontrollable bleeding
Signs of kidney problems, such as:
+ Inability to urinate
+ Changes in urine output
+ Blood in the urine
+ Sudden weight gain
Signs of low potassium levels, including:
+ Muscle pain or weakness
+ Muscle cramps
+ Abnormal heartbeat
Signs of low blood sugar, such as:
+ Dizziness
+ Headache
+ Fatigue
+ Shaking
+ Rapid heartbeat
+ Confusion
+ Hunger
+ Sweating
Chest pain or pressure
Shortness of breath, sudden weight gain, or swelling in the arms or legs
Confusion
Hallucinations (seeing or hearing things that are not there)
Seizures
Mood changes
Mouth irritation or mouth sores
Hearing loss
Changes in balance
Abnormal burning, numbness, or tingling sensations
Shakiness, difficulty moving, or stiffness
Severe and potentially life-threatening liver problems, characterized by:
+ Dark urine
+ Fatigue
+ Decreased appetite
+ Nausea or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it is essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other unusual symptoms, contact your doctor or seek medical help:
Drowsiness
Dry mouth
Stomach pain or diarrhea
Nausea or vomiting
Decreased appetite
Headache
Fatigue or weakness
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Unusual bleeding or bruising
- Fever, chills, or sore throat (signs of infection)
- Unusual tiredness or weakness
- Yellowing of the skin or eyes (jaundice)
- Dark urine or pale stools
- Severe nausea, vomiting, or diarrhea
- Skin rash or itching
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
If you have a dihydropyrimidine dehydrogenase (DPD) deficiency, a condition that affects the body's ability to break down certain medications.
This is not an exhaustive list of potential interactions. To ensure your safety, it is crucial to discuss all of your:
Prescription and over-the-counter (OTC) medications
Natural products
Vitamins
Health problems
with your doctor and pharmacist. They will help you determine whether it is safe to take this medication in combination with your other medications and health conditions. Never start, stop, or change the dosage of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
If you have a dihydropyrimidine dehydrogenase (DPD) deficiency, a condition that affects the body's ability to break down certain medications.
This is not an exhaustive list of potential interactions. To ensure your safety, it is crucial to discuss all of your:
Prescription and over-the-counter (OTC) medications
Natural products
Vitamins
Health problems
with your doctor and pharmacist. They will help you determine whether it is safe to take this medication in combination with your other medications and health conditions. Never start, stop, or change the dosage of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Regular blood tests will be necessary, as directed by your doctor, to monitor your condition. Be sure to discuss any concerns or questions you have with your doctor.
This medication may interfere with certain laboratory tests, so it is crucial to notify all your healthcare providers and laboratory personnel that you are taking this drug.
One of the potential risks associated with this medication is that it may suppress the bone marrow's ability to produce essential blood cells, leading to severe and potentially life-threatening bleeding problems or infections. If you experience any symptoms of infection, such as fever, chills, severe sore throat, ear or sinus pain, cough, increased or discolored sputum, painful urination, mouth sores, or a wound that does not heal, or if you notice any bruising or bleeding, or feel extremely tired or weak, contact your doctor immediately.
You may be more prone to bleeding while taking this medication, so it is essential to take precautions to avoid injury. Use a soft-bristled toothbrush and an electric razor to minimize the risk of bleeding. Additionally, you may be more susceptible to infections, so practice good hygiene by washing your hands frequently and avoiding close contact with people who have infections, colds, or flu.
This medication may also increase your risk of sunburn, so take necessary precautions when spending time outdoors. If you experience excessive sunburn while taking this medication, inform your doctor.
Do not take this medication for longer than prescribed, as this may increase the risk of developing a secondary infection.
If you are pregnant, planning to become pregnant, or breastfeeding, it is essential to discuss the potential benefits and risks of this medication with your doctor to ensure the best possible outcome for you and your baby.
This medication may interfere with certain laboratory tests, so it is crucial to notify all your healthcare providers and laboratory personnel that you are taking this drug.
One of the potential risks associated with this medication is that it may suppress the bone marrow's ability to produce essential blood cells, leading to severe and potentially life-threatening bleeding problems or infections. If you experience any symptoms of infection, such as fever, chills, severe sore throat, ear or sinus pain, cough, increased or discolored sputum, painful urination, mouth sores, or a wound that does not heal, or if you notice any bruising or bleeding, or feel extremely tired or weak, contact your doctor immediately.
You may be more prone to bleeding while taking this medication, so it is essential to take precautions to avoid injury. Use a soft-bristled toothbrush and an electric razor to minimize the risk of bleeding. Additionally, you may be more susceptible to infections, so practice good hygiene by washing your hands frequently and avoiding close contact with people who have infections, colds, or flu.
This medication may also increase your risk of sunburn, so take necessary precautions when spending time outdoors. If you experience excessive sunburn while taking this medication, inform your doctor.
Do not take this medication for longer than prescribed, as this may increase the risk of developing a secondary infection.
If you are pregnant, planning to become pregnant, or breastfeeding, it is essential to discuss the potential benefits and risks of this medication with your doctor to ensure the best possible outcome for you and your baby.
Overdose Information
Overdose Symptoms:
- Nausea
- Vomiting
- Diarrhea
- Abdominal pain
- Bone marrow suppression (leukopenia, thrombocytopenia, anemia)
- Hepatotoxicity
What to Do:
In case of suspected overdose, seek immediate medical attention or call a poison control center (1-800-222-1222). Management is primarily supportive. Hemodialysis can effectively remove flucytosine from the body.
Drug Interactions
Major Interactions
- Cytarabine (antagonizes the antifungal activity of flucytosine)
Moderate Interactions
- Amphotericin B (can increase flucytosine uptake into fungal cells, potentially increasing toxicity, but also synergistic antifungal effect)
- Myelosuppressive agents (increased risk of bone marrow suppression)
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with differential and platelets
Rationale: To establish baseline hematologic status due to risk of myelosuppression.
Timing: Prior to initiation of therapy.
Renal function (Serum Creatinine, BUN, Creatinine Clearance)
Rationale: Flucytosine is primarily renally eliminated; dose adjustments are necessary in renal impairment.
Timing: Prior to initiation of therapy.
Liver function tests (ALT, AST, Alkaline Phosphatase, Bilirubin)
Rationale: To establish baseline hepatic status and monitor for potential hepatotoxicity.
Timing: Prior to initiation of therapy.
Routine Monitoring
Complete Blood Count (CBC) with differential and platelets
Frequency: At least twice weekly (or more frequently if abnormalities develop)
Target: Maintain WBC > 3000/mm³, Platelets > 75,000/mm³
Action Threshold: Discontinue or reduce dose if WBC < 3000/mm³ or platelets < 75,000/mm³.
Renal function (Serum Creatinine, BUN)
Frequency: At least twice weekly (or more frequently if abnormalities develop)
Target: Maintain within normal limits or stable baseline
Action Threshold: Adjust dose if renal function declines.
Liver function tests (ALT, AST)
Frequency: Weekly (or more frequently if abnormalities develop)
Target: Maintain within normal limits or stable baseline
Action Threshold: Consider dose reduction or discontinuation if significant elevations occur.
Flucytosine serum concentrations (peak and trough)
Frequency: Periodically, especially in patients with renal impairment, severe illness, or when combined with amphotericin B.
Target: Peak: 25-100 mcg/mL; Trough: <25 mcg/mL
Action Threshold: Adjust dose to maintain levels within therapeutic range and minimize toxicity (trough >100 mcg/mL associated with increased toxicity).
Symptom Monitoring
- Signs of bone marrow suppression (unusual bleeding/bruising, fever, sore throat, fatigue)
- Gastrointestinal disturbances (nausea, vomiting, diarrhea, abdominal pain)
- Signs of liver dysfunction (yellowing of skin/eyes, dark urine, persistent nausea/vomiting)
- Skin rash
- Headache, dizziness, confusion
Special Patient Groups
Pregnancy
Flucytosine is classified as Pregnancy Category C. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal studies have shown teratogenic effects.
Trimester-Specific Risks:
First Trimester:
Potential for teratogenic effects based on animal data. Avoid if possible.
Second Trimester:
Use with caution; monitor fetal development.
Third Trimester:
Use with caution; monitor fetal development and maternal hematologic parameters.
Lactation
Flucytosine is excreted in human milk. Due to the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Infant Risk:
Risk of bone marrow suppression, gastrointestinal disturbances, and potential long-term effects. Caution advised.
Pediatric Use
Safety and efficacy have not been fully established in pediatric patients, especially neonates. Dosing is generally similar to adults on a mg/kg basis, but close monitoring of hematologic, renal, and hepatic parameters is crucial due to potential for increased toxicity and immature organ function.
Geriatric Use
Elderly patients are more likely to have decreased renal function, which necessitates careful dose adjustment and frequent monitoring of renal function and hematologic parameters to prevent drug accumulation and toxicity.
Clinical Information
Clinical Pearls
- Flucytosine is almost always used in combination with amphotericin B for serious systemic fungal infections (e.g., cryptococcal meningitis, severe candidiasis) due to synergy and to prevent resistance development.
- Therapeutic drug monitoring (TDM) of flucytosine serum levels is highly recommended, especially in patients with renal impairment, severe illness, or when combined with amphotericin B, to optimize efficacy and minimize toxicity.
- Capsules should be swallowed whole; they should not be chewed, crushed, or opened.
- Myelosuppression is the most common and serious adverse effect; frequent CBC monitoring is critical.
- Resistance can develop rapidly when flucytosine is used as monotherapy, hence the strong recommendation for combination therapy.
Alternative Therapies
- Fluconazole (for cryptococcal meningitis consolidation/maintenance, candidiasis)
- Voriconazole (for invasive aspergillosis, candidiasis)
- Isavuconazole (for invasive aspergillosis, mucormycosis)
- Posaconazole (for prophylaxis of invasive fungal infections, mucormycosis)
- Echinocandins (e.g., Caspofungin, Micafungin, Anidulafungin for candidiasis, aspergillosis)
- Amphotericin B formulations (e.g., liposomal amphotericin B)
Cost & Coverage
Average Cost:
Highly variable, typically $1000-$3000+ per 100 capsules (250mg)
Generic Available:
Yes
Insurance Coverage:
Tier 3 or 4 (Specialty Drug)
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist for more information. If you have any questions or concerns about your medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek medical attention. When seeking help, be prepared to provide details about the medication, including the amount taken and the time it happened, to ensure you receive the best possible care.